Biopsy‐proven adenoviral diarrhea responding to low‐dose cidofovir

Abstract: We present a case of diarrhea secondary to biopsy‐proven adenovirus (ADV) infection after autologous peripheral hematopoietic stem cell transplant for multiple myeloma. The patient had a negative plasma polymerase chain reaction for ADV and a dramatic clinical response to low‐dose cidofovir. To our knowledge, this is the first report in an adult hematopoietic stem cell recipient of the use of low‐dose cidofovir to treat proven ADV gastrointestinal infection.     

High diagnostic yield from transbronchial biopsy of solitary pulmonary nodules using low‐dose CT‐guidance

Background and objective: The diagnostic yield from fluoroscopy‐guided bronchoscopic transbronchial biopsy of small solitary pulmonary nodules is low. The hypothesis tested in the present study was that the diagnostic yield can be significantly increased by combining flexible bronchoscopy with CT‐guidance using a dedicated low‐dose protocol. Methods: CT‐guided transbronchial biopsies were performed in 15 patients with a newly diagnosed solitary peripheral pulmonary nodule and negative conventional bronchoscopic biopsies under fluoroscopic guidance. For imaging, a multi‐detector helical CT unit, adjusted at 120 kV, 15 mAs/slice, 4 × 5 mm collimation, 10 mm reconstructed slice thickness and a maximal scan length of 150 mm, was used. After advancing the biopsy forceps towards the lesion, a CT scan was obtained. When the tip of the forceps reached or penetrated the lesion a biopsy was taken, otherwise the procedure was repeated with a maximum of eight attempts. The effective radiation dose was calculated. Results: The average diameter of the nodules was 23 ± 6 mm (mean ± SD) with a maximum distance to the parietal pleura of 18 mm (mean 6.5 mm). A mean of 4.1 (range 2–8) CT scans was performed to localize the lesion. In four patients, the forceps only reached the periphery of the nodule. In one patient, the nodule was missed in all attempts. Histology was malignant in eight patients and benign in four patients. In three patients, biopsy results were false negative (benign or non‐specific instead of malignant). The overall diagnostic yield was 73%. Complications consisted of two pneumothoraces, one of which necessitated a chest tube. Mean effective radiation dose was 0.55 mSv (range 0.3–1.0). Conclusions: CT‐guided transbronchial biopsy can be a valuable diagnostic tool in evaluating solitary pulmonary nodules. This applies for selected patients when other diagnostic methods are either unavailable or inappropriate. The diagnostic yield is high and, when a low‐dose protocol is used, radiation exposure can be kept at a minimum.     

Clarithromycin (Biaxin)‐lenalidomide‐low‐dose dexamethasone (BiRd) versus lenalidomide‐low‐dose dexamethasone (Rd) for newly diagnosed myeloma

The objective of this case‐matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low‐dose dexamethasone (BiRd) vs. lenalidomide/low‐dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital‐Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention‐to‐treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very‐good‐partial‐response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time‐to‐progression (median 48.3 vs. 27.5 months, P = 0.071), and progression‐free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3‐year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3–4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case‐matchedanalysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

No indication of increased infection rates using low‐dose alemtuzumab instead of anti‐thymocyte globulin as graft‐versus‐host disease prophylaxis before allogeneic stem cell transplantation

Background

Alemtuzumab as part of the conditioning protocol is effective in reducing graft‐versus‐host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg).

Methods

We performed a retrospective, single‐center, case‐control study analyzing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein‐Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus‐6 (HHV6) infection using low‐dose alemtuzumab in comparison with anti‐thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation. Forty‐four patients transplanted from unrelated donors between 2001 and 2012 were matched by age, diagnosis, and conditioning regimen and treated either with alemtuzumab 10 mg at day ?2 (respectively, 20 mg in case of mismatch transplantation) or ATG. ATG Fresenius (10 mg/kg for 3 days) or Thymoglobulin (2 mg/kg for 3 days) were used.

Results

Rates of CMV reactivation, EBV reactivation, and clinical manifest HHV6 infection or toxoplasmosis did not differ significantly between both groups until 2 years after transplantation. No case of post‐transplant lymphoproliferative disorder was observed. Also, rates of neutropenic fever during inpatient treatment after transplantation did not differ significantly in both groups.

Conclusion

We saw no indication of increased infections rates when using low‐dose alemtuzumab as GvHD prophylaxis before allogeneic stem cell transplantation in this retrospective analysis.     

Complications of low‐dose,echo‐guided alcohol septal ablation

Background : Alcohol septal ablation (ASA) is a catheter‐based intervention that has been used as an alternative to surgical myectomy in highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods : This retrospective study was designed to evaluate the incidence of major complications in the mid‐term follow‐up of low‐dose (1–2.5 ml of ethanol), echo‐guided alcohol septal ablation. Results : A total of 101 consecutive patients (56 ± 15 years) with highly symptomatic HOCM were enrolled. At 6 months, there was a significant decrease in resting outflow gradient accompanied by reduction in basal septal diameter and improvement in symptoms (P < 0.01). Two patients (2%) experienced procedural ventricular tachycardias terminated by electrical cardioversion. A total of 87 patients (86%) underwent an uneventful postprocedural hospital stay. The postprocedural complete heart block occurred in 10 patients (10%), and subsequent permanent pacemaker was implanted in four cases (4%). Sustained ventricular arrhythmias requiring electrical cardioversion occurred in four patients (4%) within postprocedural hospital stay. Subsequently, ICD was not implanted in any of these cases. The patients were repeatedly examined by Holter ECG monitoring, and in the mid‐term follow‐up (6–50 months), they stayed asymptomatic and without any ventricular arrhythmias. Conclusion : This study demonstrates the same early incidence of complete heart block requiring permanent pacemaker implantation (4%) and sustained ventricular arrhythmias following low‐dose, echo‐guided ASA. © 2009 Wiley‐Liss, Inc.     

GVHD prophylaxis using low‐dose cyclosporine improves survival in leukaemic recipients of HLA‐identical sibling transplants

Graft‐versus‐host disease (GVHD) prophylaxis of short duration (6 months) with low‐dose cyclosporine A (CsA) starting at 1 mg/kg per day i.v. and four doses of methotrexate (MTX) were given to 171 consecutive leukaemic recipients of HLA‐identical sibling transplants. In contrast, apart from MTX, retrospective controls received high‐dose CsA, starting at 5–7.5 mg/kg per day i.v. and discontinued 1 yr post‐transplant. In the low‐dose CsA group, the probability of acute GVHD grades I–II (70% vs. 53%, P < 0.01), and chronic GVHD were increased (58% vs. 25%, P < 0.01), whereas the incidences of acute GVHD grades III–IV (9% vs. 5%, P = 0.62), and non‐relapse mortality (20% vs. 22%, P = 0.58) were similar. Moreover, the probability of relapse was decreased (31% vs. 54%, P < 0.01), and both relapse‐free (56% vs. 38%, P = 0.04) and overall survival (61% vs. 40%, P = 0.04) were markedly improved using the low‐dose CsA regimen. In multivariate analyses, low‐dose CsA was strongly associated with chronic GVHD [relative hazard (RH) 2.56, P < 0.01], which decreased the risk of relapse (RH 0.46, P < 0.01) and improved the probability of survival (RH 1.84, P < 0.01). In conclusion, a low‐dose CsA regimen in leukaemic recipients of HLA‐identical sibling transplants increases the rate of chronic GVHD, which seems to attenuate the risk of relapse, thereby improving patient survival owing to enhanced graft‐versus‐leukaemia effect.     

Show me the evidence: Effectiveness of low‐dose prophylaxis

Prophylaxis is the gold standard treatment for haemophilia but requires more amount of clotting factor concentrates, than on demand therapy. Low dose prophylaxis is an alternative for countries with limited resources. There are data of evidence showing the superiority of low‐dose prophylaxis than episodic treatment. Studies from China, India, Tunisia, Thailand and Indonesia reported experiences with low dose prophylaxis using outcome assessment. These studies have shown the effectiveness of various protocols regimen with once, twice or thrice injection of 10‐15 UI Kg‐1 per injection. These protocols allow reduction of joint bleeds and at least delay of joint damages. There is not enough long‐term data nowadays, but low dose prophylaxis is certainly better than on demand therapy and should be considered as a first step of prophylaxis in some countries but not the final goal.     

Prevalence of erosive esophagitis among Japanese patients taking low‐dose aspirin

Background and Aim: The risk for erosive esophagitis (EE) with low‐dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA. Methods: From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 ± 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age‐ and sex‐matched patients not taking aspirin were randomly chosen as controls (n = 159). Two well‐experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers. Results: The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7–3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5–8.8). Conclusion: In Japanese patients taking ASA, EE was not as common as peptic ulcers.     

Effects of low‐dose aspirin on endothelial function in hypertensive patients

Background: It has been reported that administration of low‐dose aspirin significantly reduces the frequency of major cardiovascular events in patients with hypertension and coronary artery disease. It is generally considered that the preventative effects of long‐term aspirin administration on major cardiovascular events are due to the inhibition of platelet aggregation. Hypothesis: It is not known whether administration of low‐dose aspirin restores endothelium‐dependent vasodilatation, and this study was undertaken to prove or disprove this question in patients with hypertension. Methods: Flow‐mediated endothelium‐dependent dilatation and glyceryl trinitrate‐induced endothelium‐independent dilatation were investigated in 18 hypertensive patients and 10 normotensive control subjects. In the hypertensive patients, flow‐mediated dilatation was investigated and cyclic guano‐sine monophosphate plasma (cGMP) was measured before and at 8 weeks after the administration of 162 mg of aspirin. Results: Flow‐mediated dilatation before aspirin administration was more reduced in the hypertensive patients than in the control subjects (6.4 ± 2.0% vs. 11.3 ± 2.3%, p< 0.0001). Glyceryl trinitrate‐induced dilatation before aspirin administration was similar in hypertensive patients and control subjects. Flow‐mediated dilatation after aspirin administration was improved compared with that before aspirin administration (10.4 ± 3.5% vs. 6.4 ± 2.0%, p<0.0004). The cGMP product after aspirin administration was significantly higher than that before aspirin administration. Conclusions: Administration of low‐dose aspirin may restore the endothelium‐dependent vasodilatation in hypertensive patients. Furthermore, increased nitric oxide production may play a partial role in the improvement in endothelial function induced by administration of low‐dose aspirin.